Colchicine-Binding Site Inhibitors from Chemistry to Clinic: A Review

O’Connor, C. (2014). Essentials of Cell Biology. Learn Science at Scitable, NPG Education. Available online: https://www.nature.com/scitable/ebooks/essentials-of-cell-biology-14749010/118240354/.

Thu, 2015, Targeting Mitosis in Cancer: Emerging Strategies, Mol. Cell, 60, 524, 10.1016/j.molcel.2015.11.006

Downing, 2000, Structural Basis for the Interaction of Tubulin with Proteins and Drugs That Affect Microtubule Dynamics, Ann. Rev. Cell Biol., 16, 89, 10.1146/annurev.cellbio.16.1.89

Cooper, G.M., Hausman, R.E., and Hausman, R.E. (2019, September 29). The Cell: A Molecular Approach, Available online: https://www.ncbi.nlm.nih.gov/books/NBK9876/.

Wilson, 1995, Microtubule Dynamics: Taking Aim at a Moving Target, Chem. Biol., 2, 569, 10.1016/1074-5521(95)90119-1

Rieder, 2004, Stuck in Division or Passing Through: What Happens When Cells Cannot Satisfy the Spindle Assembly Checkpoint, Dev. Cell, 7, 637, 10.1016/j.devcel.2004.09.002

Prota, 2014, A New Tubulin-Binding Site and Pharmacophore for Microtubule-Destabilizing Anticancer Drugs, Proc. Natl. Acad. Sci. USA, 111, 13817, 10.1073/pnas.1408124111

Maldonado, 2010, Free Tubulin Modulates Mitochondrial Membrane Potential in Cancer Cells, Cancer Res., 70, 10192, 10.1158/0008-5472.CAN-10-2429

Ahern, 1987, Does Colchicine Work? The Results of the First Controlled Study in Acute Gout, Aust. N. Z. J. Med., 17, 301, 10.1111/j.1445-5994.1987.tb01232.x

Lange, 2001, Current Aspects of Colchicine Therapy—Classical Indications and New Therapeutic Uses, Eur. J. Med. Res., 6, 150

Levy, 1991, Colchicine Prophylaxis in Familial Mediterranean Fever: Reappraisal after 15 Years, Semin. Arthritis Rheum., 20, 241, 10.1016/0049-0172(91)90019-V

Yurdakul, 2001, A Double-Blind Trial of Colchicine in Behçet’s Syndrome, Arthiritis Rheum., 44, 2686, 10.1002/1529-0131(200111)44:11<2686::AID-ART448>3.0.CO;2-H

Vaidya, 2019, The Role of Colchicine in Acute Coronary Syndromes, Clin. Therepeutics, 41, 11, 10.1016/j.clinthera.2018.07.023

Martinez, 2018, The Nlrp3 Inflammasome and the Emerging Role of Colchicine to Inhibit Atherosclerosis-Associated Inflammation, Atherosclerosis, 269, 262, 10.1016/j.atherosclerosis.2017.12.027

Rymer, 2017, Failure to Launch: Targeting Inflammation in Acute Coronary Syndromes, J. Am. Coll. Cardiol., 2, 484

Finkelstein, 2010, Colchicine Poisoning: The Dark Side of an Ancient Drug, Clin. Toxicol., 45, 407, 10.3109/15563650.2010.495348

Nogales, 1998, Structure of the Alpha-Beta Tubulin Dimer by Electron Crystallography, Nature, 391, 199, 10.1038/34465

Andreu, 1998, Role of the Colchicine Ring a and Its Methoxy Groups in the Binding to Tubulin and Microtubule Inhibition, Biochemistry, 37, 8356, 10.1021/bi9728553

Ravelli, 2004, Insight into Tubulin Regulation from a Complex with Colchicine and a Stathmin-Like Domain, Nature, 428, 198, 10.1038/nature02393

Prota, 2014, The Novel Microtubule-Destabilizing Drug Bal27862 Binds to the Colchicine Site of Tubulin with Distinct Effects on Microtubule Organization, J. Mol. Biol., 426, 1848, 10.1016/j.jmb.2014.02.005

Dong, M., Liu, F., Zhou, H., Zhai, S., and Yan, B. (2016). Novel Natural Product- and Privileged Scaffold-Based Tubulin Inhibitors Targeting the Colchicine Binding Site. Molecules, 21.

Taylor, J.B., and Triggle, D.J. (2007). Comprehensive Medicinal Chemistry II. 7.04 Microtubule Targeting Agents; 7.04.2.2.1 Colchicine and Analogs, Available online: https://www.sciencedirect.com/science/article/pii/B008045044X002054.

NCI National Cancer Institute (2019, November 16). Angiogenesis Inhibitors, Available online: https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/angiogenesis-inhibitors-fact-sheet#why-is-angiogenesis-important-in-cancer.

Denekamp, 1984, Vascular Endothelium as the Vulnerable Element in Tumours, Acta Radiol. Oncol., 23, 217, 10.3109/02841868409136015

Thorpe, 2003, The First International Conference on Vascular Targeting: Meeting Overview, Cancer Res., 63, 1144

Denekamp, 1982, Endothelial Cell Proliferation as a Novel Approach to Targeting Tumour Therapy, Br. J. Cancer, 45, 136, 10.1038/bjc.1982.16

Waghray, 2018, Inhibit or Evade Multidrug Resistance P-Glycoprotein in Cancer Treatment, J. Med. Chem., 61, 5108, 10.1021/acs.jmedchem.7b01457

Stengel, 2010, Class 111 Beta-Tubulin Expression and in Vitro Resistance to Microtubule Targeting Agents, Br. J. Cancer, 102, 316, 10.1038/sj.bjc.6605489

Watt, J.M., and Breyer-Brandwijk, M.G. (1962). Medicinal Poisonous Plants Southern Eastern Africa, Livingstone. [2nd ed.].

Kanthou, 2002, The Tumor Vascular Targeting Agent Combretastatin a–4-Phosphate Induces Reorganization of the Actin Cytoskeleton and Early Membrane Blebbing in Human Endothelial Cells, Blood, 99, 2060, 10.1182/blood.V99.6.2060

Hua, 2003, Oxi4503, a Novel Vascular Targeting Agent: Effects on Blood Flow and Antitumor Activity in Comparison to Combretastatin a-4 Phosphate, Anticancer Res., 23, 1433

Pettit, 1989, Isolation and Structure of the Strong Cell Growth and Tubulin Inhibitor Combretastatin a-4, Experientia, 45, 209, 10.1007/BF01954881

Siemann, 2004, Vascular-Targeting Therapies for Treatment of Malignant Disease, Cancer, 100, 2491, 10.1002/cncr.20299

McGown, 1990, Differential Cytotoxicity of Combretastatins A1 and A4 in Two Daunorubicin-Resistant P388 Cell Lines, Cancer Chemother. Pharmacol., 26, 79, 10.1007/BF02940301

Baguley, 1991, Inhibition of Growth of Colon 38 Adenocarcinoma by Vinblastine and Colchicine: Evidence for a Vascular Mechanism, Eur. J. Cancer Clin. Oncol., 27, 482, 10.1016/0277-5379(91)90391-P

Hill, 1993, Vinca Alkaloids: Anti-Vascular Effects in a Murine Tumour, Eur. J. Cancer, 29, 1320, 10.1016/0959-8049(93)90082-Q

Dark, 1997, Combretastatin a-4, an Agent That Displays Potent and Selective Toxicity toward Tumor Vasculature, Cancer Res., 57, 1829

Chaplin, 2002, The Development of Combretastatin A4 Phosphate as a Vascular Targeting Agent, Int. J. Radiat. Oncol. Biol. Phys., 54, 1491, 10.1016/S0360-3016(02)03924-X

Kremmidiotis, 2010, Bnc105: A Novel Tubulin Polymerization Inhibitor That Selectively Disrupts Tumor Vasculature and Displays Single-Agent Antitumor Efficacy, Mol. Cancer Ther., 9, 1562, 10.1158/1535-7163.MCT-09-0815

Siemann, 2008, Dual Targeting of Tumor Vasculature: Combining Avastin and Vascular Disrupting Agents (Ca4p or Oxi4503), Anticancer Res., 28, 2027

Tozer, 2008, Tumour Vascular Disrupting Agents: Combating Treatment Resistance, Br. J. Radiol., 81, 12, 10.1259/bjr/36205483

Pettit, 2005, Antineoplastic Agents. 445. Synthesis and Evaluation of Structural Modifications of (Z)- and (E)-Combretastatin a-4, J. Med. Chem., 48, 4087, 10.1021/jm0205797

Ohsumi, 1998, Syntheses and Antitumor Activity of Cis-Restricted Combretastatins: 5-Membered Heterocyclic Analogues, Bioorg. Med. Chem. Lett., 8, 3153, 10.1016/S0960-894X(98)00579-4

Lee, 2008, 1,2,3,4-Tetrahydro-2-Thioxopyrimidine Analogs of Combretastatin-A4, Eur. J. Med. Chem., 43, 2011, 10.1016/j.ejmech.2007.11.030

Gaspari, 2017, Structural Basis of Cis- and Trans-Combretastatin Binding to Tubulin, Chem, 2, 102, 10.1016/j.chempr.2016.12.005

Gomtsyan, 2012, Heterocycles in Drugs and Drug Discovery, Chem. Heterocycl. Compd., 48, 7, 10.1007/s10593-012-0960-z

Nguyen, 2012, Synthesis and Biological Evaluation of Novel Heterocyclic Derivatives of Combretastatin a-4, Bioorg. Med. Chem. Lett., 22, 7227, 10.1016/j.bmcl.2012.09.047

Herdman, 2016, Synthesis and Biological Evaluation of Benzocyclooctene-Based and Indene-Based Anticancer Agents That Function as Inhibitors of Tubulin Polymerization, MedChemComm, 7, 2418, 10.1039/C6MD00459H

Ecker, 2009, Synthesis and Antitumor-Evaluation of Cyclopropyl-Containing Combretastatin Analogs, Bioorg. Med. Chem. Lett., 19, 6948, 10.1016/j.bmcl.2009.10.064

Wang, 2002, Potent, Orally Active Heterocycle-Based Combretastatin a-4 Analogues:  Synthesis, Structure−Activity Relationship, Pharmacokinetics, and in Vivo Antitumor Activity Evaluation, J. Med. Chem., 45, 1697, 10.1021/jm010523x

Mateo, 2005, Stilbenophane Analogues of Deoxycombretastatin a-4, J. Org. Chem., 70, 6544, 10.1021/jo0508393

Daniel, 2017, Review of Cytotoxic Ca4 Analogues That Do Not Target Microtubules: Implications for Ca4 Development, Mini-Rev. Med. Chem., 17, 1507

Greene, 2015, Combretastatins: More Than Just Vascular Targeting Agents?, J. Pharmacol. Exp. Ther., 355, 212, 10.1124/jpet.115.226225

Siemann, 2009, A Review and Update of the Current Status of the Vasculature Disabling Agent Combretastatin-A4 Phosphate (Ca4p), Expert Opin. Investig. Drugs, 18, 189, 10.1517/13543780802691068

Lu, 2012, An Overview of Tubulin Inhibitors That Interact with the Colchicine Binding Site, Pharm. Res., 29, 2943, 10.1007/s11095-012-0828-z

Ducki, 2007, The Development of Chalcones as Promising Anticancer Agents, Investig. Drugs J., 10, 42

Ducki, 2009, Combretastatin-Like Chalcones as Inhibitors of Microtubule Polymerization. Part 1: Synthesis and Biological Evaluation of Antivascular Activity, Bioorg. Med. Chem., 17, 7698, 10.1016/j.bmc.2009.09.039

Pettit, 1998, Antineoplastic Agents. 379. Synthesis of Phenstatin Phosphate 1a, J. Med. Chem., 41, 1688, 10.1021/jm970644q

Pommery, 2011, In Vitro Metabolism of Phenstatin: Potential Pharmacological Consequences, Drug Metab. Lett., 5, 209, 10.2174/187231211796904973

Winn, 2017, Bioreductively Activatable Prodrug Conjugates of Phenstatin Designed to Target Tumor Hypoxia, Bioorg. Med. Chem. Lett., 27, 636, 10.1016/j.bmcl.2016.11.093

Messaoudi, 2009, Isocombretastatins a Versus Combretastatins A: The Forgotten Isoca-4 Isomer as a Highly Promising Cytotoxic and Antitubulin Agent, J. Med. Chem., 52, 4538, 10.1021/jm900321u

Zhang, 2006, The Synthetic Compound Cc-5079 Is a Potent Inhibitor of Tubulin Polymerization and Tumor Necrosis Factor-Α Production with Antitumor Activity, Cancer Res., 66, 951, 10.1158/0008-5472.CAN-05-2083

Vu, 2010, Cc-5079: A Small Molecule with Mkp1, Antiangiogenic, and Antitumor Activity, J. Surg. Res., 164, 116, 10.1016/j.jss.2009.01.031

Wen, 2015, 3-(3,4,5-Trimethoxyphenylselenyl)-1h-Indoles and Their Selenoxides as Combretastatin a-4 Analogs: Microwave-Assisted Synthesis and Biological Evaluation, Eur. J. Med. Chem., 90, 184, 10.1016/j.ejmech.2014.11.024

Zuo, 2015, 3-(3-Hydroxy-4-Methoxyphenyl)-4-(3,4,5-Trimethoxyphenyl)-1,2,5-Selenadiazole (G-1103), a Novel Combretastatin a-4 Analog, Induces G2/M Arrest and Apoptosis by Disrupting Tubulin Polymerization in Human Cervical Hela Cells and Fibrosarcoma Ht-1080 Cells, Chem.-Biol. Interact., 227, 7, 10.1016/j.cbi.2014.12.016

Guan, 2014, Synthesis and Biological Evaluation of Novel 3,4-Diaryl-1,2,5-Selenadiazol Analogues of Combretastatin a-4, Eur. J. Med. Chem., 87, 1, 10.1016/j.ejmech.2014.09.046

Hamel, 2013, Synthesis and Evaluation of Diaryl Sulfides and Diaryl Selenide Compounds for Antitubulin and Cytotoxic Activity, Bioorg. Med. Chem. Lett., 23, 4669, 10.1016/j.bmcl.2013.06.009

Pang, 2017, Design, Synthesis, and Biological Evaluation of Novel Selenium-Containing Isocombretastatins and Phenstatins as Antitumor Agents, J. Med. Chem., 60, 7300, 10.1021/acs.jmedchem.7b00480

Greene, 2016, Synthesis and Biochemical Evaluation of 3-Phenoxy-1,4-Diarylazetidin-2-Ones as Tubulin-Targeting Antitumor Agents, J. Med. Chem., 59, 90, 10.1021/acs.jmedchem.5b01086

Banik, 2003, Stereoselective Synthesis of Β-Lactams with Polyaromatic Imines:  Entry to New and Novel Anticancer Agents, J. Med. Chem., 46, 12, 10.1021/jm0255825

Sun, 2004, Examination of the 1,4-Disubstituted Azetidinone Ring System as a Template for Combretastatin a-4 Conformationally Restricted Analogue Design, Bioorg. Med. Chem. Lett., 14, 2041, 10.1016/j.bmcl.2004.02.050

Wang, S., Malebari, A.M., Greene, T.F., O’Boyle, N.M., Fayne, D., Nathwani, S.M., Twamley, B., McCabe, T., Keely, N.O., and Zisterer, D.M. (2019). 3-Vinylazetidin-2-Ones: Synthesis, Antiproliferative and Tubulin Destabilizing Activity in Mcf-7 and Mda-Mb-231 Breast Cancer Cells. Pharmaceuticals, 12.

Carr, 2011, Synthesis, Biochemical and Molecular Modelling Studies of Antiproliferative Azetidinones Causing Microtubule Disruption and Mitotic Catastrophe, Eur. J. Med. Chem., 46, 4595, 10.1016/j.ejmech.2011.07.039

Carr, 2010, Synthesis and Evaluation of Azetidinone Analogues of Combretastatin a-4 as Tubulin Targeting Agents, J. Med. Chem., 53, 8569, 10.1021/jm101115u

Carr, 2010, Lead Identification of Conformationally Restricted Β-Lactam Type Combretastatin Analogues: Synthesis, Antiproliferative Activity and Tubulin Targeting Effects, Eur. J. Med. Chem., 45, 5752, 10.1016/j.ejmech.2010.09.033

Malebari, 2017, Β-Lactam Analogues of Combretastatin a-4 Prevent Metabolic Inactivation by Glucuronidation in Chemoresistant Ht-29 Colon Cancer Cells, Eur. J. Med. Chem., 130, 261, 10.1016/j.ejmech.2017.02.049

Rustin, 2003, Phase I Clinical Trial of Weekly Combretastatin A4 Phosphate: Clinical and Pharmacokinetic Results, J. Clin. Oncol., 21, 2815, 10.1200/JCO.2003.05.185

Cummings, 2004, Glucuronidation as a Mechanism of Intrinsic Drug Resistance in Colon Cancer Cells: Contribution of Drug Transport Proteins, Biochem. Pharmacol., 67, 31, 10.1016/j.bcp.2003.07.019

Fu, 2017, Structure-Activity Relationship Studies of Β-Lactam-Azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site, Sci. Rep., 7, 12788, 10.1038/s41598-017-12912-4

Macdonough, 2013, Synthesis and Biological Evaluation of Indole-Based, Anti-Cancer Agents Inspired by the Vascular Disrupting Agent 2-(3′-Hydroxy-4′-Methoxyphenyl)-3-(3″,4″,5″-Trimethoxybenzoyl)-6-Methoxyindole (Oxi8006), Bioorg. Med. Chem., 21, 6831, 10.1016/j.bmc.2013.07.028

Kamal, 2015, Synthesis of Phenstatin/Isocombretastatin–Chalcone Conjugates as Potent Tubulin Polymerization Inhibitors and Mitochondrial Apoptotic Inducers, Org. Biomol. Chem., 13, 3963, 10.1039/C4OB02606C

Maguire, 2018, Synthesis of Dihydronaphthalene Analogues Inspired by Combretastatin a-4 and Their Biological Evaluation as Anticancer Agents, MedChemComm, 9, 1649, 10.1039/C8MD00322J

Dohle, 2018, Quinazolinone-Based Anticancer Agents: Synthesis, Antiproliferative Sar, Antitubulin Activity, and Tubulin Co-Crystal Structure, J. Med. Chem., 61, 1031, 10.1021/acs.jmedchem.7b01474

Rastogi, 2018, Photoresponsive Azo-Combretastatin a-4 Analogues, Eur. J. Med. Chem., 143, 1, 10.1016/j.ejmech.2017.11.012

Sheldon, 2016, Photoswitchable Anticancer Activity Via Trans–Cis Isomerization of a Combretastatin a-4 Analog, Org. Biomol. Chem., 14, 40, 10.1039/C5OB02005K

Engdahl, 2015, Synthesis, Characterization, and Bioactivity of the Photoisomerizable Tubulin Polymerization Inhibitor Azo-Combretastatin A4, Org. Lett., 17, 4546, 10.1021/acs.orglett.5b02262

Broichhagen, 2015, A Roadmap to Success in Photopharmacology, Acc. Chem. Res., 48, 1947, 10.1021/acs.accounts.5b00129

Velema, 2014, Photopharmacology: Beyond Proof of Principle, J. Am. Chem. Soc., 136, 2178, 10.1021/ja413063e

Fehrentz, 2011, Optochemical Genetics, Angew. Chem. Int. Ed., 50, 12156, 10.1002/anie.201103236

Wang, 2018, Structural Modification of the 3,4,5-Trimethoxyphenyl Moiety in the Tubulin Inhibitor Veru-111 Leads to Improved Antiproliferative Activities, J. Med. Chem., 61, 7877, 10.1021/acs.jmedchem.8b00827

Chen, 2012, Discovery of Novel 2-Aryl-4-Benzoyl-Imidazole (Abi-Iii) Analogues Targeting Tubulin Polymerization as Antiproliferative Agents, J. Med. Chem., 55, 7285, 10.1021/jm300564b

Chen, 2011, Synthesis and Antiproliferative Activity of Novel 2-Aryl-4-Benzoyl-Imidazole Derivatives Targeting Tubulin Polymerization, Bioorg. Med. Chem., 19, 4782, 10.1016/j.bmc.2011.06.084

Kashyap, 2019, Therapeutic Efficacy of a Novel Βiii/Βiv-Tubulin Inhibitor (Veru-111) in Pancreatic Cancer, J. Exp. Clin. Cancer Res., 38, 29, 10.1186/s13046-018-1009-7

Hwang, 2015, Structural Optimization of Indole Derivatives Acting at Colchicine Binding Site as Potential Anticancer Agents, ACS Med. Chem. Lett., 6, 993, 10.1021/acsmedchemlett.5b00208

Wang, 2019, Structure-Guided Design, Synthesis, and Biological Evaluation of (2-(1h-Indol-3-Yl)-1h-Imidazol-4-Yl)(3,4,5-Trimethoxyphenyl) Methanone (Abi-231) Analogues Targeting the Colchicine Binding Site in Tubulin, J. Med. Chem., 62, 6734, 10.1021/acs.jmedchem.9b00706

Romagnoli, 2012, Synthesis and Evaluation of 1,5-Disubstituted Tetrazoles as Rigid Analogues of Combretastatin a-4 with Potent Antiproliferative and Antitumor Activity, J. Med. Chem., 55, 475, 10.1021/jm2013979

Romagnoli, 2019, Design, Synthesis and Biological Evaluation of Novel Vicinal Diaryl-Substituted 1h-Pyrazole Analogues of Combretastatin a-4 as Highly Potent Tubulin Polymerization Inhibitors, Eur. J. Med. Chem., 181, 111577, 10.1016/j.ejmech.2019.111577

Salvador, 2005, New Naphthylcombretastatins. Modifications on the Ethylene Bridge, Bioorg. Med. Chem., 13, 2097, 10.1016/j.bmc.2005.01.012

Dupuis, 2003, Saquinavir Induces Stable and Functional Expression of the Multidrug Transporter P-Glycoprotein in Human Cd4 T-Lymphoblastoid Cemrev Cells, HIV Med., 4, 338, 10.1046/j.1468-1293.2003.00169.x

Lai, 2018, Design, Synthesis and Biological Evaluation of a Novel Tubulin Inhibitor 7a3 Targeting the Colchicine Binding Site, Eur. J. Med. Chem., 156, 162, 10.1016/j.ejmech.2018.05.010

Ana, 2019, Synthesis and Evaluation of Antiproliferative Microtubule-Destabilising Combretastatin A-4 Piperazine Conjugates, Org. Biomol. Chem., 17, 6184, 10.1039/C9OB00558G

Choi, 2001, Expression Profile of Histone Deacetylase 1 in Gastric Cancer Tissues, Jpn. J. Cancer Res., 92, 1300, 10.1111/j.1349-7006.2001.tb02153.x

Boyle, 2011, Designed Multiple Ligands for Cancer Therapy, Curr. Med. Chem., 18, 4722, 10.2174/092986711797535344

Schmitt, F., Gosch, L.C., Dittmer, A., Rothemund, M., Mueller, T., Schobert, R., Biersack, B., Volkamer, A., and Höpfner, M. (2019). Oxazole-Bridged Combretastatin a-4 Derivatives with Tethered Hydroxamic Acids: Structure⁻Activity Relations of New Inhibitors of Hdac and/or Tubulin Function. Int. J. Mol. Sci., 20.

Khelifi, 2017, Design, Synthesis and Anticancer Properties of Isocombretaquinolines as Potent Tubulin Assembly Inhibitors, Eur. J. Med. Chem., 127, 1025, 10.1016/j.ejmech.2016.11.012

Patil, 2016, Indole Molecules as Inhibitors of Tubulin Polymerization: Potential New Anticancer Agents, an Update (2013–2015), Future Med. Chem., 8, 1291, 10.4155/fmc-2016-0047

Patil, 2012, Indole Molecules as Inhibitors of Tubulin Polymerization: Potential New Anticancer Agents, Future Med. Chem., 4, 2085, 10.4155/fmc.12.141

Brancale, 2007, Indole, a Core Nucleus for Potent Inhibitors of Tubulin Polymerization, Med. Res. Rev., 27, 209, 10.1002/med.20080

Li, 2019, Design, Synthesis and Biological Evaluation of Quinoline-Indole Derivatives as Anti-Tubulin Agents Targeting the Colchicine Binding Site, Eur. J. Med. Chem., 163, 428, 10.1016/j.ejmech.2018.11.070

Naret, 2019, 1,1-Diheterocyclic Ethylenes Derived from Quinaldine and Carbazole as New Tubulin-Polymerization Inhibitors: Synthesis, Metabolism, and Biological Evaluation, J. Med. Chem., 62, 1902, 10.1021/acs.jmedchem.8b01386

Niu, 2019, Structure Guided Design, Synthesis, and Biological Evaluation of Novel Benzosuberene Analogues as Inhibitors of Tubulin Polymerization, J. Med. Chem., 62, 5594, 10.1021/acs.jmedchem.9b00551

Mustafa, 2019, Potent Combretastatin a-4 Analogs Containing 1,2,4-Triazole: Synthesis, Antiproliferative, Anti-Tubulin Activity, and Docking Study, Eur. J. Med. Chem., 183, 111697, 10.1016/j.ejmech.2019.111697

King, 1946, The Similarity of the Effect of Podophyllin and Colchicine and Their Use in the Treatment of Condylomata Acuminata, Science, 104, 244, 10.1126/science.104.2698.244

Kern, 1950, Podophyllin in the Treatment of Cutaneous Carcinoma, JAMA Dermatol., 62, 526, 10.1001/archderm.1950.01530170052006

Canel, 2000, Podophyllotoxin, Phytochemistry, 54, 115, 10.1016/S0031-9422(00)00094-7

1991, The Chemical and Biological Route from Podophyllotoxin Glucoside to Etoposide: Ninth Cain Memorial Award Lecture, Cancer Res., 51, 5

(2019, December 24). FDA Vumon® (Teniposide Injection), Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020119s010s011lbl.pdf.

Duca, 2005, Synthesis and Biological Study of a New Series of 4‘-Demethylepipodophyllotoxin Derivatives, J. Med. Chem., 48, 593, 10.1021/jm0495733

Keating, 2010, Rituximab: A Review of Its Use in Chronic Lymphocytic Leukaemia, Low-Grade or Follicular Lymphoma and Diffuse Large B-Cell Lymphoma, Drugs, 70, 1445, 10.2165/11201110-000000000-00000

Saulnier, 1994, Synthesis of Etoposide Phosphate, Bmy-40481: A Water-Soluble Clinically Active Prodrug of Etoposide, Bioorg. Med. Chem. Lett., 4, 2567, 10.1016/S0960-894X(01)80285-7

Hande, 1998, Etoposide: Four Decades of Development of a Topoisomerase Ii Inhibitor, Eur. J. Cancer, 34, 1514, 10.1016/S0959-8049(98)00228-7

Viel, 1974, Antitumor Chemotherapy. Ix. Cytotoxic Activity in Cultured Tumor Cells of Chalcone Substituants and Related Compounds, Journal de Pharmacie de Belgique, 29, 341

Peyrot, 1992, Mechanism of Binding of the New Antimitotic Drug Mdl 27048 to the Colchicine Site of Tubulin: Equilibrium Studies, Biochemistry, 31, 11125, 10.1021/bi00160a024

Yang, 2014, Synthesis and Biological Evaluation of Novel Millepachine Derivatives as a New Class of Tubulin Polymerization Inhibitors, J. Med. Chem., 57, 7977, 10.1021/jm500849z

Cao, 2013, Synthesis and Biological Evaluation of Novel Pyranochalcone Derivatives as a New Class of Microtubule Stabilizing Agents, Eur. J. Med. Chem., 62, 579, 10.1016/j.ejmech.2013.01.007

Yang, 2018, The Compound Millepachine and Its Derivatives Inhibit Tubulin Polymerization by Irreversibly Binding to the Colchicine-Binding Site in Β-Tubulin, J. Biol. Chem., 293, 9461, 10.1074/jbc.RA117.001658

Engel, 2015, Hope and Disappointment: Covalent Inhibitors to Overcome Drug Resistance in Non-Small Cell Lung Cancer, ACS Med. Chem. Lett., 7, 2, 10.1021/acsmedchemlett.5b00475

Tan, 2014, Development of Covalent Inhibitors That Can Overcome Resistance to First-Generation Fgfr Kinase Inhibitors, Proc. Natl. Acad. Sci. USA, 111, 4869, 10.1073/pnas.1403438111

Lindamulage, 2017, Novel Quinolone Chalcones Targeting Colchicine-Binding Pocket Kill Multidrug-Resistant Cancer Cells by Inhibiting Tubulin Activity and Mrp1 Function, Sci. Rep., 7, 10298, 10.1038/s41598-017-10972-0

Greene, 2013, Synthesis and Biochemical Activities of Antiproliferative Amino Acid and Phosphate Derivatives of Microtubule-Disrupting Β-Lactam Combretastatins, Eur. J. Med. Chem., 62, 705, 10.1016/j.ejmech.2013.01.016

Moldoveanu, 2014, Many Players in Bcl-2 Family Affairs, Trends Biochem. Sci., 39, 101, 10.1016/j.tibs.2013.12.006

Li, 2019, Discovery of Novel Quinoline–Chalcone Derivatives as Potent Antitumor Agents with Microtubule Polymerization Inhibitory Activity, J. Med. Chem., 62, 993, 10.1021/acs.jmedchem.8b01755

Hamel, 1996, Antimitotic Natural Products and Their Interactions with Tubulin, Med. Res. Rev., 16, 207, 10.1002/(SICI)1098-1128(199603)16:2<207::AID-MED4>3.0.CO;2-4

Wipf, 2004, Chemistry and Biology of Curacin, A, Curr. Pharm. Des., 10, 1417, 10.2174/1381612043384853

Lu, 2011, Design, Synthesis, and Sar Studies of 4-Substituted Methoxylbenzoyl-Aryl-Thiazoles Analogues as Potent and Orally Bioavailable Anticancer Agents, J. Med. Chem., 54, 4678, 10.1021/jm2003427

(2019, November 10). RCSB 6NNG Tubulin-Rb3_Sld-Ttl in Complex with Compound DJ95. Available online: https://www.rcsb.org/structure/6NNG.

Arnst, 2019, Colchicine Binding Site Agent Dj95 Overcomes Drug Resistance and Exhibits Antitumor Efficacy, Mol. Pharmacol., 96, 73, 10.1124/mol.118.114801

Matei, 2009, Activity of 2 Methoxyestradiol (Panzem® Ncd) in Advanced, Platinum-Resistant Ovarian Cancer and Primary Peritoneal Carcinomatosis: A Hoosier Oncology Group Trial, Gynecol. Oncol., 115, 90, 10.1016/j.ygyno.2009.05.042

LaVallee, 2008, Significant Antitumor Activity In Vivo Following Treatment with the Microtubule Agent Enmd-1198, Mol. Cancer Ther., 7, 1472, 10.1158/1535-7163.MCT-08-0107

Pasquier, 2010, Enmd-1198, a New Analogue of 2-Methoxyestradiol, Displays Both Antiangiogenic and Vascular-Disrupting Properties, Mol. Cancer Ther., 9, 1408, 10.1158/1535-7163.MCT-09-0894

Esteve, 2010, Abstract 1977: Bal27862: A Unique Microtubule-Targeted Drug That Suppresses Microtubule Dynamics, Severs Microtubules, and Overcomes Bcl-2- and Tubulin Subtype-Related Drug Resistance, Cancer Res., 70, 1977, 10.1158/1538-7445.AM10-1977

Zheng, 2014, Design, Synthesis, and Biological Evaluation of Novel Pyridine-Bridged Analogues of Combretastatin-A4 as Anticancer Agents, J. Med. Chem., 57, 3369, 10.1021/jm500002k

Zheng, 2016, A Novel Nitrobenzoate Microtubule Inhibitor That Overcomes Multidrug Resistance Exhibits Antitumor Activity, Sci. Rep., 6, 31472, 10.1038/srep31472

Bai, 2017, BZML, a Novel Colchicine Binding Site Inhibitor, Overcomes Multidrug Resistance in A549/Taxol Cells by Inhibiting P-Gp Function and Inducing Mitotic Catastrophe, Cancer Lett., 402, 81, 10.1016/j.canlet.2017.05.016

Gourdeau, 2004, Antivascular and Antitumor Evaluation of 2-Amino-4-(3-Bromo-4,5-Dimethoxy-Phenyl)-3-Cyano-4-Chromenes, a Novel Series of Anticancer Agents, Mol. Cancer Ther., 3, 1375, 10.1158/1535-7163.1375.3.11

Liu, 2018, Synthesis and Biological Evaluation of 4,6-Diphenyl-2-(1h-Pyrrol-1-Yl)Nicotinonitrile Analogues of Crolibulin and Combretastatin a-4, Eur. J. Med. Chem., 146, 185, 10.1016/j.ejmech.2018.01.052

Xiao, 2006, The Sulindac Derivatives Osi-461, Osip486823, and Osip487703 Arrest Colon Cancer Cells in Mitosis by Causing Microtubule Depolymerization, Mol. Cancer Ther., 5, 60, 10.1158/1535-7163.MCT-05-0260

Haanen, 2001, Sulindac and Its Derivatives: A Novel Class of Anticancer Agents, Curr. Opin. Investig. Drugs, 2, 677

Clinicaltrials Gov (2019, September 19). 6 Studies Found For: CP 461/Osi-461, Available online: https://clinicaltrials.gov/ct2/results?cond=&term=CP+461&cntry=&state=&city=&dist=.

Pettit, 2000, Antineoplastic Agents 429. Syntheses of the Combretastatin a-1 and Combretastatin B-1 Prodrugs, Anti-Cancer Drug Des., 15, 203

Tozer, 2002, The Biology of the Combretastatins as Tumour Vascular Targeting Agents, Int. J. Exp. Pathol., 83, 21, 10.1046/j.1365-2613.2002.00211.x

Kirwan, 2004, Comparative Preclinical Pharmacokinetic and Metabolic Studies of the Combretastatin Prodrugs Combretastatin A4 Phosphate and A1 Phosphate, Clin. Cancer Res., 10, 1446, 10.1158/1078-0432.CCR-0518-03

Mooney, 2009, A Phase Ii Trial of Fosbretabulin in Advanced Anaplastic Thyroid Carcinoma and Correlation of Baseline Serum-Soluble Intracellular Adhesion Molecule-1 with Outcome, Thyroid, 19, 233, 10.1089/thy.2008.0321

Griggs, 2001, Targeting Tumour Vasculature: The Development of Combretastatin A4, Lancet Oncol., 2, 82, 10.1016/S1470-2045(00)00224-2

EMA (2016). Public Summary of Opinion on Orphan Designation, EMA. Fosbretabulin Tromethamine for the Treatment of Gastro-Entero-Pancreatic Neuroendocrine Tumours.

EMA (2013). Public Summary of Opinion on Orphan Designation, EMA. Fosbretabulin Tromethamine for the Treatment of Ovarian Cancer.

Therepeutics, M. (2019, October 28). Developing Innovative Therapeutic Approaches to Treat Cancer; Oxi4503. Available online: http://www.mateon.com/product-development/taboxi4503/.

Kim, 2007, Antitumor and Antivascular Effects of Ave8062 in Ovarian Carcinoma, Cancer Res., 67, 9337, 10.1158/0008-5472.CAN-06-4018

Morinaga, 2003, Combination Effect of Ac-7700, a Novel Combretastatin a-4 Derivative, and Cisplatin against Murine and Human Tumors in Vivo, Cancer Sci., 94, 200, 10.1111/j.1349-7006.2003.tb01419.x

Blay, 2015, Ombrabulin Plus Cisplatin Versus Placebo Plus Cisplatin in Patients with Advanced Soft-Tissue Sarcomas after Failure of Anthracycline and Ifosfamide Chemotherapy: A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial, Lancet Oncol., 16, 531, 10.1016/S1470-2045(15)70102-6

Munshi, 2010, Arq 197, a Novel and Selective Inhibitor of the Human C-Met Receptor Tyrosine Kinase with Antitumor Activity, Mol. Cancer Ther., 9, 1544, 10.1158/1535-7163.MCT-09-1173

Graveel, 2013, Met: A Critical Player in Tumorigenesis and Therapeutic Target, Cold Spring Harb. Perspect. Biol., 5, a009209, 10.1101/cshperspect.a009209

Aoyama, 2014, Tivantinib (Arq 197) Exhibits Antitumor Activity by Directly Interacting with Tubulin and Overcomes Abc Transporter–Mediated Drug Resistance, Mol. Cancer Ther., 13, 2978, 10.1158/1535-7163.MCT-14-0462

Clincialtrials Gov (2019, November 25). Tivantinib: Phase 3, Available online: https://clinicaltrials.gov/ct2/results?term=tivantinib&age_v=&gndr=&type=&rslt=&phase=2&Search=Apply.

Cabibbo, 2010, A Meta-Analysis of Survival Rates of Untreated Patients in Randomized Clinical Trials of Hepatocellular Carcinoma, Hepatology, 51, 1274, 10.1002/hep.23485

Sangro, 2017, Nivolumab in Patients with Advanced Hepatocellular Carcinoma (Checkmate 040): An Open-Label, Non-Comparative, Phase 1/2 Dose Escalation and Expansion Trial, Lancet, 389, 2492, 10.1016/S0140-6736(17)31046-2

Rimassa, 2018, Tivantinib for Second-Line Treatment of Met-High, Advanced Hepatocellular Carcinoma (Metiv-Hcc): A Final Analysis of a Phase 3, Randomised, Placebo-Controlled Study, Lancet Oncol., 19, 682, 10.1016/S1470-2045(18)30146-3

(2019, November 25). KyowaKirin Kyowa Hakko Kirin Announces Discontinuation for Developing Arq 197 (Tivantinib). Available online: https://www.kyowakirin.com/media_center/news_releases/2017/e20171006_01.html.

Prior, 2012, A Comprehensive Survey of Ras Mutations in Cancer, Cancer Res., 72, 2457, 10.1158/0008-5472.CAN-11-2612

(2019, November 25). Beyondspring’s Novel Study 103 Phase 3 Design in Nsclc Presented at 2019 Iaslc World Conference on Lung Cancer. Available online: https://www.globenewswire.com/.

(2019, November 20). An Open-Label Study of Intravenous Bal101553 in Adult Patients with Solid Tumors, Available online: https://clinicaltrials.gov/ct2/show/record/NCT01397929.

Calvert, 2013, A First-in-Human (Fih) Dose-Escalation Study of the Safety, Pharmacokinetics (Pk), and Pharmacodynamics (Pd) of Intravenous Bal101553, a Novel Microtubule Inhibitor, in Adult Patients with Advanced Solid Tumors, J. Clin. Oncol., 31, 2566, 10.1200/jco.2013.31.15_suppl.2566

Kolb, 2015, Initial Testing (Stage 1) of Bal101553, a Novel Tubulin Binding Agent, by the Pediatric Preclinical Testing Program, Pediatr. Blood Cancer, 62, 1106, 10.1002/pbc.25329

(2019, December 18). Lisavanbulin and Radiation Therapy in Treating Patients with Newly Diagnosed Glioblastoma, Available online: https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2016-01847&r=1.

Clincialtrials Gov (2019, December 18). A Phase 1/11 Trial of Crolibulin (Epc2407) Plus Cisplatin in Adults with Solid Tumors with a Focus on Anaplastic Thyroid Cancer (Atc), Available online: https://clinicaltrials.gov/ct2/show/NCT01240590.